Guice began his career with fanzine work and "designing patches and emblems for a small company in North Carolina."[4] His first credited comics work was penciling and inking the independently published The Crusaders #1 (November 1982), although he had previously ghosted for Pat Broderick on Rom Annual #1 (1982).[5] On the strength of his fanzine work, (and, Guice believes, at the behest of Rom Annual writer Bill Mantlo) Marvel editor Al Milgrom offered him a tryout on the toy-spin-off title Micronauts. Referring to Rom Annual #1 and Micronauts #48 (Dec. 1982), he remarked that "[b]oth were breaking points for me getting into comics".[4]

Guice's cover for Doctor Strange #15 (March 1990) used Christian music singer Amy Grant's likeness without her permission,[9] leading to her management filing a complaint against Marvel Comics, saying the cover gave the appearance she was associating with witchcraft. A US District Court sealed an out-of-court settlement between Grant and Marvel in early 1991, with a consent decree that Marvel did not admit to any liability or wrongdoing.[10][11][12]

Towards the end of 1995, Guice moved to Valiant Comics, becoming the regular penciller of Eternal Warrior. Guice penciled part of the Sliders: Narcotica comic book, based on the TV series Sliders and written by the show's star Jerry O'Connell. Having Guice draw the series was:

"a personal treat for Jerry [O'Connell] as "Butch" Guice (as he used to be called during his successful run at Marvel Comics) was a favorite of his during his comic-reading years."[15]

In March 2000, Guice became the artist on Birds of Prey for issues #15 to #34. In addition, Guice drew a "Robin and Oracle" story in Batman: Gotham City Secret Files and Origins and the Universe X Spidey one-shot, from Marvel. After his run on Birds of Prey, Guice left DC Comics and moved to Tampa, Florida to work for CrossGen. He was brought in to launch Ruse with writer Mark Waid, in November 2001. Effectively a Victoriansteampunkdetective story, although set on an analogue of Earth in the far-distant future, and part of CrossGen's 'Sigilverse'. Guice continued as the penciller of Ruse until its cancellation with #26 (January 2004). Guice resigned from CrossGen "just prior to the layoffs" and before the remaining staff were released from "exclusivity status".[3]

Writer Geoff Johns, "one of Humanoids' biggest supporters from the very beginning of [their] US publishing program," pitched a story with Kris Grimminger featuring "every great monster from Greek mythology, from Medusa to the Stymphalian Birds."[3] Humanoids editor Paul Benjamin began the search "throughout the world for a great artist who would appeal to both an American and a European audience. Butch was always on our mind for the book, but he was busy drawing Ruse for CrossGen. We began talking to Butch once he became available and Olympus was a perfect fit."[3]

Guice said of Humanoids and Olympus:

"I've been interested in working with Paul Benjamin and Humanoids for several years now... [their] approach to their material, both in quality and design of product as well as the extensive worldwide market they've cultivated with a variety of genres, held enormous interest for me. After my resignation from the CrossGen staff, I contacted Paul and we started talking about possibilities. Once I read the two scripts for Olympus, I knew it was exactly the type of thing I would enjoy drawing. Having it be written by Geoff and Kris was a very pleasurable bonus."[3]

Although intended as two volumes, to date, only the first has seen print. This is likely due to the lapsing of Humanoids US-distribution deal with DC,[18] as Guice said in December 2003, while working on Volume One that that book "wraps in March [2004]", which him then "scheduled to start work on volume two almost immediately".[3]

After leaving CrossGen, Guice worked with writer Warren Ellis on a six-issue story-arc entitled "New Maps of Hell" for DC's JLA: Classified title and then worked on the "One Year Later" revamp of Aquaman, in Kurt Busiek's Aquaman: Sword of Atlantis, debuting with #40 of the previous Aquaman title.[5] Guice stayed for eight issues, and Busiek said of his artist colleague:

"Aside from being a terrific artist and strong storyteller, Butch can really make you believe in the exotic fantasy worlds of the Atlantic oceanscape. And he draws a great King Shark -- and a creepy Dweller, to boot. And cool warriors, gorgeous women, strange creatures and more. He's the perfect guy for this book, and I've wanted to work with him for years."[19]

In 2007, Guice provided rotating art duties for The Invincible Iron Man, with issue #19-20's World War Hulk tie-in issue and became inker on Captain America for #32-34, and then taking over full duties as of #35. Guice penciled a miniseries taking place in the Ultimate Universe, entitled Ultimate Origins written by Brian Michael Bendis. Bendis wrote of Guice "I've been a fan of his for years and years, and when I saw what he was doing in Iron Man [with Gage]... I had to have him."[20] Guice was the penciler on the Wildstorm mini-series Storming Paradise, written by Chuck Dixon.

^DeFalco, Tom; Gilbert, Laura, ed. (2008). "1980s". Marvel Chronicle A Year by Year History. London, United Kingdom: Dorling Kindersley. p. 227. ISBN978-0756641238. The original X-Men gathered in X-Factor #1 by Bob Layton and artist Jackson Guice.

^Manning, Matthew K.; Dolan, Hannah, ed. (2010). "1980s". DC Comics Year By Year A Visual Chronicle. London, United Kingdom: Dorling Kindersley. p. 228. ISBN978-0-7566-6742-9. Written by Mike Baron, with art by Jackson Guice, the Flash's new adventures began with his twentieth birthday party.

^Manning, Matthew K. "1990s" in Gilbert (2008), p. 251: "This first part [of the 'Days of Future Present' storyline], written by Walter Simonson, with art by Jackson Guice, marked the debut of Ahab, a denizen from this alternate future."

^Manning "1990s" in Dolan, p. 259: " The issue also featured four teaser comics that introduced a group of contenders all vying for the Superman name...The Eradicator returned in a preview tale by writer Roger Stern and artist Jackson Guice."

^Manning "1990s" in Dolan, p. 279: "The writing team of Andy Lanning and Dan Abnett alongside the art of Jackson "Butch" Guice introduced readers to a new kind of hero in Resurrection Man."

^Manning, Shaun (June 1, 2005). "Olympus". ComicsBulletin.com. Archived from the original on November 23, 2008. Retrieved March 3, 2012. [Olympus Vol. 1] looks to be one of the final books of the DC/Humanoids partnership...